Management of acute, life-threatening neurologic illnesses, such as severe traumatic brain injury, is facilitated by accurate and continuous monitoring of cerebral oxygenation. However, current monitoring systems are invasive, requiring either cannulation of the internal jugular venous bulb or insertion of a probe directly into the brain. Although relatively low-risk, continuous jugular venous bulb monitoring is technically arduous. Near-infrared spectroscopy, a noninvasive method of monitoring cerebral blood oxygenation, is promising, but has yet to provide quantitative measurement in adults. At present there is no system for accurate, non-invasive, and continuous monitoring of cerebral blood oxygenation. We proposed and performed in vitro and in vivo testing of a novel optoacoustie sensor that accurately and continuously measures blood oxygenation directly from the superior sagittal sinus, a structure that can easily be localized due to the high resolution of the optoacoustic technique. The optoacoustic technique is based on generation of ultrasonic (optoacoustic) waves by laser pulses and detection of these waves by a sensitive acoustic transducer. Optoacoustic monitoring of blood oxygenation utilizes well-established differences in the optical absorption coefficients of oxy- and deoxyhemoglobin in the near-infrared spectral range. During our current NIH R21 project (supported under Program Announcement PA-98-050 directed at the development of innovative technologies including photoacoustic brain monitoring), we designed, built, and tested a portable, noninvasive optoacoustic system for accurate monitoring of cerebral blood oxygenation. Our in vitro and in vivo (in sheep) studies demonstrated that: (1) the parameters of the optoacoustic waves are linearly dependent on blood oxygenation; (2) the use of specially designed transducers and optoacoustic probes allows sensitive detection despite optical and acoustic attenuation by thick bone; and (3) this technique can measure blood oxygenation with high accuracy. In this grant application, we propose to further develop this sensor by testing it clinically. The specific aims of the project are: (1) to evaluate the sensor in cadavers; (2) to develop an algorithm for calculating oxygen saturation on-line in vivo in volunteers; and (3) to validate the sensor performance in a second group of volunteers. By the end of the project the sensor will be developed sufficiently to permit multi-center clinical evaluation. In addition to brain monitoring, the proposed sensor can potentially be used for local non-invasive measurement of blood oxygenation in other organs.